We propose to use a newly developed, sensitive, specific radiometric 2-step radioimmunoassay for thyroglobulin -antithyroglobulin immune complex (TgA) to study circulating levels of TgA in patients with Graves' disease, Hashimoto's thyroiditis and primary myxedema, to compare these levels with those of thyroglobulin (Tg), antithyroglobulin, anti-(thyroid)microsomal antibody, long acting thyroid stimulator (LATS), and thyroid stimulating immunoglobulin (TSI), in the same subjects, and to determine whether TgA levels are correlated with the development of presence of ophthalmopathy or pretibial myxedema. We will monitor the distribution and fate of TgA administered to rats and rabbits, using the new assay and whole body scintigraphy. In addition, attempts will be made to further characterize and purify the component of human and bovine extraocular muscle membrane to which human Tg and TgA bind in vitro. BIBLIOGRAPHIC REFERENCES: Studies on the pathogenesis of Grave's opthalmopathy (with some related observations regarding therapy). J.P. Kriss, J. Konishi and M. Herman. Recent Progress in Hormone Research 31:533, 1975. Purification of human anti-thyroglobulin. Y. Takeda, S. Thomas, G. Johnson, and J.P. Kriss. J. Clin. Endocr. and Metab. 41: 738, 1975.